Download - Endocrine and metabolic disorders
ENDOCRINE AND METABOLIC DISORDERS
RCW Wong
Endocrine and metabolic disorders
Endocrine glands regulate homeostasis by secretion of hormones which affect many organ systems
Metabolism - process body uses to get or make energy from food.
Metabolic disorders occur when abnormal chemical reactions disrupt this process.
too much or too little of some substances occurs when some organs, e.g. liver or pancreas,
become diseased or do not function normally.
Endocrine glands
Hypothalamus Pituitary Pineal Thyroid Parathyroid Thymus Pancreas Adrenal Sex organsMainly regulated in negative feedback loop
Endocrine disorders Pituitary tumours –gigantism,
acromegaly, diabetes insipidus Diabetes mellitus Adrenal insufficiency Thyroid disorders- hypo or hyperthyroid Parathyroid-hypo or hyper Tumours- multiple endocrine neoplasia,
phaeochromocytoma
Inherited disorders of metabolism
Acid lipase disease Barth syndrome Central pontine
myelinosis Phenylketonuria Lesch-Nyhan disease G6PD deficiency Pompe disease Mitochondrial
myopathies Muscular dystrophy
Lipid storage disease Mucolipidosis Mucopolysaccharidos
is Porphyria Hereditary fructose
intolerance Type I glycogen
storage disease Hypercholesterolemi
a Diabetes mellitus
type I
Acquired disorders of metabolism
Diabetes mellitus Type II Hypercholesterolemia Metabolic syndrome /Syndrome X
Important disorders Diabetes mellitus Adrenocortical hypofunction Thyroid disorders G6PD
Diabetes mellitus
Diabetes mellitus Diabetes mellitus (DM) is a heterogenous
disorder of metabolism due to absolute or relative deficiency of insulin
It affects 9% of the population aged 18-69 years in Singapore causing multi-organ damage and dysfunction
Associated with 9.3% of all deaths National Health Survey 1998, Epidemiology and Disease Control, Department of Ministry of Health, Singapore.
Classification of diabetes Type 1 (primary diabetes-insulin
dependant diabetes mellitus)-due to severe insulin deficiency caused by destruction of the pancreatic beta cells
Type 2 (primary diabetes -non-insulin dependent diabetes mellitus)-due to varying degrees of insulin resistance and insulin deficiency
Classification of diabetes Gestational diabetes-diabetes that is first
recognized or occurs during pregnancy Miscellanous group- includes diabetes
caused by chronic pancreatitis, drugs like steroids, hemochromatosis, acromegaly
Signs and Symptomsof diabetes mellitus
Type I mainly juvenile and occasionally non-obese individuals/elderly when hyperglycaemia first appears
Polyuria Polydipsia Rapid weight loss associated with
hyperglycaemia Postural hypotension Muscle weakness Ketoacidosis Ketonuria
Signs and Symptomsof diabetes mellitus
Type II (mainly over 40 and obese) Polyuria Polydipsia Non-ketotic form of diabetes Candidal vaginitis in women Chronic skin infections Generalized pruritus Associated with hypertension, hyperlipidemia
and atherosclerosis
Known risk factors positive family history Hypertension Overweight previous gestational diabetes impaired glucose tolerance plasma HDL-cholesterol less than
0.9mmol/L and plasma trigylceride above 2.8 mmol/L
Diagnosis Based on clinical history symptoms and lab analysis
Lab analysisUrinanalysis: a) Glucosuria- certain drugs like salicylates,
ascorbic acids can give false negative results. A normal renal threshold and a reliable bladder is essential for interpretation.
b) KetonuriaCapillary blood glucose measurements by
bedside (Hypocount) in a hospital setting requires rigorous quality control programs and certification of personnel to avoid errors
Lab analysis Fasting plasma glucose- Repeated fasting
plasma glucose over 7 mmol/L and /or random plasma glucose over 11 mmol/L in an asymptomatic individual is enough for diagnosis. In symptomatic persons, only one of the above values is required.
Glucose tolerance test: gold standard for diagnosis of diabetes but not always necessary
Lab analysis Glycosylated haemoglobin (HbA1c): HbA1c is
abnormally high in diabetics with chronic hyperglycaemia. The normal value should be 4-6% of total haemoglobin. This reflects the state of gycaemia in the preceeding 8-12 weeks
Attempts to use this for diagnosis of diabetes are controversial as the sensitivity in detecting diabetes with this test is only 85% i.e. diabetes cannot be excluded by a normal value. However, elevated levels are quite specific (91%) in identifying diabetes
Therapy for type 1 diabetes consists of dietary management and insulin.
Therapy for type 2 diabetes consists of dietary management and possibly oral hypoglycemic agents or insulin
Management of diabetic pts
The clinician should assess the disease severity, including the presence of chronic complications of DM e.g. IHD, renal disorders, neuropathy.
The degree of control, the types of medication (dosage, duration) and past history of acute infections and hospital admissions should be noted.
Minor surgery/outpatients Routine dental treatment or minor oral
surgery (under local anaesthesia [LA]) can be carried out in well-controlled diabetics
Schedule such patients first thing in the morning after breakfast and after their routine anti-diabetic medication
Minor surgery/outpatients Keep appointments short; watch out for signs of
hypoglycaemia (in the dental setting, a collapse of a known diabetic is usually due to hypoglycaemia since ketoacidosis takes some time to develop).
Onset of hypoglycaemia requires termination of the procedure and administration of a sweetened drink.
If unconscious, give 1mg glucagon IM followed by a glucose drink. Alternatively, if an IV line can be secured, give 50ml of 50% dextrose intravenously
Minor surgery/outpatients Diabetic ketoacidosis (DKA) occurs in
patients with type 1 disease because of stress or worsening glucose control, which produces hyperglycemia that causes osmotic diuresis, leading to severe dehydration and hyponatremia
Minor surgery/outpatients Post-operative antibiotics may be
considered after surgical procedures, if infection is a concern
If patients are unable to take their normal diet post-operatively, their insulin or oral hypoglycaemic medication may need to be reduced. Patients must be told to monitor their blood glucose at home, as is usually done.
GA/ major surgery For diabetics/pts with
hyperglycaemia/suspected diabetes undergoing major oral surgery procedures (under GA), consultation with the anaesthetist and physician/endocrinologist is essential.
A regime needs to be worked out to ensure good blood glucose control preoperatively, perioperatively and postoperatively. (Glucose/Insulin Sliding scale)
Start hypocount measurements 6 hourly and target insulin therapy on a sliding scale.
Sliding Scale insulin protocol
Hypocount readings (mmol/L)
Subcutaneous insulin dosage
4-6 4 units 6.1-8
6 units
8.1-10 8 units 10.1-12 10 unitsMore than 12 12 units
Adrenocortical hypofunction
Introduction Medulla secretes epinephrine and
norepinephrine into adrenal veins when stimulated
Cortex secretes steroids regulating metabolism, vascular tone, cardiac contractility, TBW/Na/K balance, androgenic function
Adrenal Physiology Cyclic secretion controlled by time of day,
HPA axis, renin-angiotensin system, serum potassium levels
Stress increases basal glucocorticoid and mineralcorticoid levels 5-10 fold Occurs within minutes
Adrenal Failure Basal failure results in adrenal
insufficiency Leads to insidious wasting disease
Stress failure results in adrenal crisis Life-threatening Absence of glucocorticoids is most critical
Corticosteroids Three classes (by effect):
GlucocorticoidsMineralcorticoidsAndrogenic steroids
Glucocorticoids Regulate fat, glucose, protein metabolism Catecholamine and b-adrenergic receptor
synthesis Maintain vascular tone and cardiac
contractility Control endothelial integrity/vascular
permeability
Glucocorticoids Cortisol
Controlled by HPA axis Hypothalamus CRH and arginine
vasopressin in circadian rhythm (max 2-4am) Anterior Pituitary ACTH Adrenal cortex cortisol Peak @ 8am; declines throughout day
Glucocorticoids Cortisol
25mg produced daily (non-stressed) 5-10% free and physiologically active Remainder bound to cortisol-binding globulin
Becomes uncoupled in times of stress Negatively feeds back to control
hypothalamus Role in adrenal insufficiency
Adrenal Insufficiency Primary = failure of adrenal glands Secondary = failure of HPA axis
Usually due to chronic exogenous glucocorticoid administration
pituitary failure Tertiary = Hypothalamic dysfunction
Primary Adrenal Insufficiency
Loss of all three types of adrenal steroids 90% of glands must be destroyed to
manifest clinically High functional reserve
Adrenoleukodystrophy = X-linked inherited d/o of very-long-chain fatty acid metabolism Progressive neurological symptoms from
demyelination
Primary Adrenal Insufficiency
Addison disease = autoimmune Thrombosis/hemorrhage Sepsis, DIC, antiphospholipid syndrome
Infiltrative diseases Bilateral cancer metastasis Amyloidosis, hemosiderosis (rare)
Primary Adrenal Insufficiency
TB = m.c. infectious cause worldwide HIV = m.c. infectious cause in US
50% have degree of destruction Only 5% have clinical symptoms of A.I. CMV infection, ketoconazole use, macrophage-
released cytokines are risk factors
Secondary Adrenal Insufficiency
HPA axis failure deficiency of glucocorticoids and adrenal
androgens mineralcorticoids are unaffected
#1 cause=chronic exogenous glucocorticoid suppresses diurnal CRH/AV release both time- and dose-related reversible
recovery may take up to a year
Secondary Adrenal Insufficiency
Less common causes Postpartum necrosis (Sheehan syndrome) Adenoma hemorrhage(s) Pituitary destruction from head trauma typically have associated focal neurological
changes, visual deficits, diabetes insipidus or panhypopituitarism
Secondary Adrenal Insufficiency
MYTHBUSTERS! Short course (2-3 weeks) is unlikely to
suppress the HPA axis Daily doses of prednisone 5mg or less
are unlikely to cause secondary insufficiency
Management adrenocortical crisis and collapse if the
patient is subjected to trauma, stress (pain/ anxiety induced), and general anaesthesia
The associated medical condition which required the patient to be placed on systemic corticosteroids can complicate dental care as well. This includes asthma, autoimmune disorders and recipients of organ transplant
Management Patients on systemic corticosteroids or
those who have had steroids within the previous year may need supplemental steroid for “stressful” clinical procedures (extensive dental procedures, oral surgery).
Steroid supplementation is not normally required for routine dental procedures.
Management Stress reducing protocols should be
implemented which involve achieving good pain control intraoperatively and postoperatively
Blood pressure should be monitored during procedure and post-operatively (half-hourly for two hours post-operatively)
ManagementCorticosteroid supplementation may be
considered in : patients currently on systemic
corticosteroids patients who were on systemic
corticosteroids in the past 2 weeks to one month or who have been on it for more than one month in the past year where the amount of corticosteroids taken above is/was more than the equivalent of 7.5mg prednisolone daily
Corticosteroid cover regime
Treatment under LA (routine non-surgical dental treatment)
No supplementation required
Treatment under LA (minor Oral Surgery)
Double oral steroid dose* or give 25-50mg hydrocortisone hemisuccinate IV
Treatment under GA The target is for 50-100mg hydrocortisone hemisuccinate (within 1 hr of surgery) and 24-48 hrs post-operatively.Given as :Pre-op: 100mg hydrocortisone IV on inductionPost-op: 50mg hydrocortisone IV 8hrly
* oral dose to be taken within 2hrs of surgery
Adrenal CrisisCLINICAL PRESENTATION Life-threatening emergency May be primary or secondary HYPOTENSION
Typically resistant to catecholamine and IV fluid resuscitation
THYROID DISORDERSHYPERTHYROIDISMHYPOTHYROIDISM
THYROID HORMONES Metabolism in all body organs Stimulate the heart
heart rate stroke volume cardiac output blood flow
HYPERTHYROIDISMINCREASED THYROID HORMONES: Hypermetabolism sympathetic nervous system activity Effects protein, lipid and carbohydrate
metabolism
EFFECTS ON PROTEIN METABOLISM
Protein synthesis and degradation More breakdown than buildup Leads to loss of protein Called negative nitrogen balance
EFFECTS ON GLUCOSE Glucose tolerance decreased Leads to hyperglycemia
EFFECTS ON FAT METABOLISM fat metabolism body fat appetite food intake; food intake does not meet
energy demands weight nutritional deficiencies with prolonged
disease
CAUSES OF HYPERTHYROIDISM
1. Graves disease2. TOXIC MULTINODULAR GOITER: multiple
thyroid nodules, milder disease3. EXOGENOUS HYPERTHYROIDISM:
excessive use of thyroid replacement hormones
4. THYROID STORM: untreated or poorly controlled hyperthyroidism; life threatening
WHO GETS IT Most often women between 20-40 yrs
ASSESSMENT Recent wgt loss Increased appetite Increase in # BM/day ****heat intolerance Diaphoresis even when temperatures
comfortable for others Palpitations/chest pain Dyspnea with or without exertion
ASSESSMENTVISUAL PROBLEMS MAY BE EARLIEST
PROBLEM: Infiltrative Exophthalmopathy (abnormal
eye appearance or function) Blurring/double vision/tiring of eyes Increased tears Photophobia Eyelid retraction(eyelid lag) Globe lag (eyeball lag)
GOITER Thyroid gland may be 4 X normal Bruits (turbulence from increased blood
flow) heard with stethoscope
CARDIAC PROBLEMS systolic BP tachycardia dysrhythmia
FURTHER SYMPTOMS Fine, soft, silky hair Smooth, moist skin Muscle weakness Hyperactive deep tendon reflexes Tremors of hands Restless, irritable, mood swings Decreased attention span Fatigued, inability to sleep
LABORATORY ASSESSMENTIN HYPERTHYROIDISM: T3 T4 TSH in Graves disease Radioactive Thyroid Scan Ultrasonography: used to determine
goiter or nodules ECG: tachycardia
DRUG THERAPY ***antithyroid drugs: thioamides
propylthiouracil (PTU) methimazole (Tapazole) carbimazole (Neo-Mercazole)
ACTION: blocks thyroid hormone production; takes time
control of cardiac manifestations (tachycardia, palpitations, diaphoresis, anxiety) until hormone production reduced: beta-adrenergic blocking drugs: propranolol (Inderal, Detensol)
DRUG THERAPYIodine preparations: Lugol’s Solution SSKI (saturated solution of potassium
iodide) Potassium iodide tablets, solution, and
syrupACTION:
decreases blood flow through the thyroid gland
This reduces the production and release of thyroid hormone
Takes about 2 wks for improvement Leads to hypothyroidism
DRUG THERAPY Lithium Carbonate ACTION: inhibits thyroid hormone release NOT USED OFTEN BECAUSE OF SIDE
EFFECTS: depressions, diabetes insipidus, tremors
DRUG THERAPYRADIOACTIVE IODINE THERAPY: Receives RAI in form of oral iodine Takes 6-8 Weeks for symptomatic relief Additional drug therapy used during this
type of treatment Not used on pregnant women
SURGICAL MANAGEMENTWhy use surgery? Used to remove large goiter causing
tracheal or esophageal compression Used for pts who do not have good
response to antithyroid drugsTWO TYPES OF SURGERIES: 1. Total thyroidectomy (must take lifelong
thyroid hormone replacement)2. Subtotal thyroidectomy
Dental management of hyperthyroid pt
The patient’s current clinical disease state, the degree of control and stability, the current medication and the presence of associated complications such as cardiac disease should be established and documented. If there is any suspicion that the disease is poorly controlled, defer dental treatment and consult the physician.
Dental management of hyperthyroid pt
Avoid any dental treatment for patients with thyrotoxicosis until the condition is stabilised
Routine dental treatment can be carried out for patients who have well-controlled disease (euthyroid) without concurrent medical problems
Aim for short, stress and pain free dental sessions.
Dental management of hyperthyroid pt
Minimise or avoid use of vasoconstrictors (especially those with uncontrolled or poorly controlled disease)
Some patients may have concurrent cardiac problems such as atrial fibrillation. These patients may be warfarinised and there may be risk for persistent bleeding. Consult physician
Carbimazole has been known to cause agranulocytosis. This may present with fever and abrupt onset of oropharyngeal ulcerations. Refer to physician
Dental management of hyperthyroid pt
A thyroid storm, an uncommon event in the dental outpatient setting, is an acute exacerbation of the hyperthyroid state
Known provoking factors include infection/sepsis, major surgical and GA procedures, pain/anxiety and abrupt discontinuation of anti-thyroid medication (and b-blockers)
Clinical presentations are extreme irritability/nervousness, increase in body temperature and risk of developing life-threatening cardiac arrthymias. This is a medical emergency requiring expert attention.
Hypothyroidism- Causes Cells damaged; no longer function Cells might be normal, person doesn’t
ingest enough iodide & tyrosine needed to make thyroid hormones
SYMPTOMS Blood levels of thyroid hormones are low Decreased metabolic rate Hypothalamus and anterior pituitary
gland make stimulatory hormones (TSH) as compensation
Thyroid gland enlarges forming goiter
MYXEDEMA DEVELOPS With low metabolism metabolites build up
inside the cells which increases mucous and water leading to cellular edema
Edema changes client’s appearance Nonpitting edema appears everywhere
especially around the eyes, hands, feet, between shoulder blades
Tongue thickens, edema forms in larynx, voice husky
INCIDENCE OF HYPOTHYROIDISM
30-60 yrs of age Mostly women
ASSESSMENT
Increased sleeping (14-16 hours daily) Generalized weakness Anorexia Muscle aches Paresthesias Constipation Cold intolerance Decreased libido, woman:difficulty
becoming pregnant, changes in menses;men/impotence
ASSESSMENT Coarse features Edema around eyes and face Blank expression Thick tongue Overall muscle movement is slow Lethargic, apathetic, drowsy, poor
attention span, poor memory
LABORATORY ASSESSMENT T3 T4 TSH
TREATMENTLIFELONG THYROID HORMONE
REPLACEMENT levothyroxine sodium (Synthroid, T4,
Eltroxin) IMPORTANT: start at low does, to avoid
hypertension, heart failure and MI Teach about S&S of hyperthyroidism with
replacement therapy
Dental management of hypothyroid pt
Stable, well controlled hypothyroid pts do not need any special precautions for routine dental treatment under LA
Avoid routine prescribing of CNS depressants in severe untreated hypothyroidism for example, benzodiazepines and narcotic analgesics as they may result in over-reactions like CNS, CVS and respiratory overdepression. Judicious use in euthyroid individuals should not be a major problem
Myxedema coma (hypothermia, bradycardia, hypotension) can be precipitated by infections, surgery, GA and drugs mentioned above
MYEXEDEMA COMA Rare serious complication of untreated
hypothyroidism Decreased metabolism causes the
heart muscle to become flabby Leads to decreased cardiac output Leads to decreased perfusion to brain
and other vital organs Leads to tissue and organ failure LIFE THREATENING EMERGENCY WITH
HIGH MORTALITY RATE
PROBLEMS SEEN WITH MYXEDEMA COMA
Coma Respiratory failure Hypotension Hyponatremia Hypothermia hypoglycemia
G6PD deficiency
WHAT IS IT?
• An inherited condition in which patients are excessively susceptible to the development of hemolytic anemia. It is the most common enzymatic disorder of RBCs in humans.
• • Affected individuals lack the ability to tolerate
biochemical oxidative stress, and red cell hemolysis is the most important clinical consequence.
• First noted in African-American soldiers who developed acute hemolytic anemia with hemoglobinuria following primaquine ingestion.
WHO WORKING GROUPS
• Class I: severely deficient, associated with chronic nonspherocytic hemolytic anemia
• Class II: severely deficient (1%-10% residual activity), associated with acute intermittent hemolytic anemia (G6PD Mediterranean)
• Class III: moderately deficient (10%-60% residual activity) - intermittent hemolysis usu assoc with infection or drugs (G6PD A)
• Class IV: normal activity (60%-150%)
• Class V: increased activity (>150%)
WHO GETS IT?
An X-linked disorder that therefore typically affects men.
Over 400 million people worldwide affected with highest prevalence in individuals of African, Mediterranean and Asian heritage. Since this is an X-linked gene, prevalence among females is higher but they are generally asymptomatic.
**Confers anti-malarial protection - unknown mechanism
How does it present?
Usually asymptomatic but can also vary from episodic anemia to chronic hemolysis. The presentation depends on the biochemistry of the variant. There are over 500 different mutations identified thus far.
acute hemolytic anemia congenital nonsperocytic hemolytic anemia neonatal hyperbilirubinemia favism
Acute hemolytic anemia
Asymptomatic at steady state without anemia or abnormal morphology.
Sudden destruction of deficient erythrocytes 2-4 days after offending "event" leads to jaundice, pallor, dark urine, +/- back pain. Abrupt drop in H/H to <4 g/dL and PBS with microspherocytes, cell fragments or bite cells. Sequestration of damaged red cells in liver and spleen.
Increase in reticulocytes within 5 days, maximal at 7-10 days with reversal of anemia even without removal of offending drug.
In G6PD Mediterranean, hemolysis more severe and can continue even after drug d/c'd.
HOW DOES IT WORK?
• G6PD is required by all cells to protect from damage by oxidation. It catalyses the first step in the HMP pathway (glucose-6-P oxidized to 6-phosphogluconate) which is linked to the reduction of NADP to NADPH, which is used to generate reduced glutathione.
• • For the red cell, this is the sole source of
protection against oxidant damage in the form of free radicals generated by the conversion of oxy- to deoxyhemoglobin and by peroxides generated by phagocytosing granulocytes.
•
cont'd
Normal red cells generate NADPH in response to oxidant stress; this capacity is impaired in patients with G6PD deficiency. Failure to withstand oxidant stress damage to sulphydryl groups in hemoglobin and the red cell membrane causes hemolysis. Cells in other tissues and organs have alternate pathways for the generation of NADPH and can withstand such oxidant stress. But not so in the simple RBC.
The activity of all red cell enzymes, including G6PD, is highest in young red cells (reticulocytes), and progressively declines as the cell ages.
PRECIPITANTS
• Infections (salmonella, E.coli, beta-hemolytic strep, rickettsiae, viral hepatitis)
• Medications (next slide)
• Metabolic abnormalities (DKA)
Pharmacological Class
Drugs
Analgesics Aspirin (acetylsalicyclic acid)Phenacetin (acetophenetidin)
Antibiotics Quinolones:ciprofloxacin,moxifloxacin, norfloxacin, ofloxacin, nalidixic acid)Sulphonamides and Sulfones:co-trimoxazole (Bactrim)sulphapyridine, sulphadimidine, sulphacetamide, sulphanilamide, sulphoxone, sulphafurazonedapsone.Others:nalidixic acidnitrofurans chloramphenicolp-aminosalicylic acid
Antimalarials chloroquine, primaquine, pamaquine
Cardiovascular procainamide, quinidine
Miscellaneous vitamin Cvitamin K analoguesmethylene bluetoluidine blueprobenecidnaphthalene (mothballs)